The overall objective of this project is to provide a virologic characterization of a new in vitro erythroid transformation system in a manner that will lead to a better understanding of virus-induced leukemogenesis. During the past year, signficant progress has been made in characterizing this system. New knowledge has been gained in three areas: (1) The relative roles of MuLV and SFFV in the in vitro erythroid transformation were examined. We have gathered data that indicate that SFFV is competent for erythroid transformation in vitro but requires MuLV for its replication. (2) We have demonstrated that the in vitro erythroid transformation is under genetic control at the FV-1 locus. (3) A number of additional viral isolates have been shown to be capable of hemopoietic cell transformation in vitro. One of these isolates, the anemia-induced strain of Friend virus (FVA), produced bursts which were significantly different from those produced by the polycythemia-inducing strain (FVP). The FVA bursts appeared to poliferate extensively but were grossly under-hemoglobinized when compared to FVP bursts. When the hormone, erythropoietin, (Epo) was added to the virus-infected cultures, virtually all the observed bursts were full hemoglobinized. We now propose to confirm and extend these observations in the following experiments: (1) We will attempt to prove that the defective SFFV is competent for transformation by the isolation of transformed cells which do not produce infectious virus (i.e. non-producer clones). Individual clones of erythroid cells will be selected and co-cultivated with fibroblast cell cultures to allow for virus amplification. After two passages, the fibroblast cell culture supernatants will be assayed for virus production. We anticipate that this method will allow us to determine that certain bursts produce virus (i.e. producers) and the others do not (non-producers). (2) We will complete our genetic analysis of the FV-1 locus by an examination of other resistant and susceptible mice as well as the F1 hybrids from these strains. Other genetic loci will also be examined. These include the FV-2, W, and Steel loci. (3) A major effort will be made to follow up our observations that the anemia-inducing strain induced bursts which were under-hemoglobinized in the absence of Epo, but finally hemoglobinized in the presence of the hormone. The (Text Truncated - Exceeds Capacity)